REACTIONS  OF  COUMALINIC  ACID  AND 
PREPARATION  OF  ITS  CHLORIDE 


BY 


BENJAMIN  WEINPER 


THESIS 


FOR  THE 


DEGREE  OF  BACHELOR  OF  SCIENCE 


IN 

CHEMICAL  ENGINEERING 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 


UNIVERSITY  OF  ILLINOIS 


1922 


UNIVERSITY  OF  ILLINOIS 


May  _ _2  5^_  1 £12  2_  1 9 2 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 


ENTITLED 3B£T  I.QtLS  _ OF.il  OUPAL  XJ XC_  AC  ID_  TI 

QF_I_TS_CHLORI_DE_. 

IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
DEGREE  OF BMm.PR__0F  .SCIEIiCJ I L. 


Instructor  in  Charge 


Approved 


HEAD  OF  DEPARTMENT  OF 


Acknowledgement . 

The  author  wishes  to  express  his  sincere  thanks 
and  gratitude  to  Dr. B.L. Souther  for  his  kind  suggestions 
and  helpful  encouragement  during  this  work. 


Table  of  Contents 


Pag- 

Historical 

1 

Alpha  Tyrones 

r 

Theoretical 

0 

Experimental 

Coumalinie  Acid 

8 

Methyl  Coumalinate 

1C 

Methyl - Chi or o -Coumalinate 

12 

Furane  2:4  Di carboxylic  Acid 

13 

Summary 

14 

Digitized  by  the  Internet  Archive 
in  2016 


https://archive.org/details/reactionsofcoumaOOwein 


HISTORICAL 


Alpha  Pyrones 

Alpha  pyrones  have  been  prepared  h y several  general 
methods.  First, by  the  action  of  concentrated  sulphuric  acid 
on  an  aldehyde  acid  or  a ketonie  acid.  For  example , ooumal ini c 
acid  (I)  was  prepared  in  the  following  v nner: 

CHOH 


CHOHCOOH 

CHp 

I 

COOK 


CH  CH 

I I 

COOK  OH 


ri-rr^TT 


# V 

HC  uHCOOH 


/ \ 

HC  CGUUri 


-►  | 

KOOC 


r.  oh 

S / 


From  acetoacetic  acid, isodehydracetic  acid  (IV)  was  obtained 
and  in  a. similar  manner  ace tonedi carboxylic  acid  gave  citra- 

coumalinic  acid  (III), 

Second, by  the  addition  of  B-ketonie  esters  and  certain 
ketones  to  esters  of  acetylenic  acids.  Lesoxy benzoin  added  to 
ethyl  phenylpropiolate  giving  4:5:6  triphenyl  alpha  pyrone  (XV ) . 

CH0C6H5 
COCoHc 


CC5H5 


CCOOC2H5 


CC^Hn 

J X 


'D 


OG 


‘0  - tj 

V 


Acetylacetone  and  benzoylacetone  in  like  manner  gave  respect- 
ively 4-phenyl-6-methyl-5-aceto  alpha  pyrone  (XVI ) and 
4-phenyl -5 -ben zoy 1-6-methyl  alpha  pyrone  (XVII)  or  4:6  di- 
phenyl-5-acetyl  alpha  pyrone  (jtVIl) . In  the  latter  case  the 
formula  of  the  compound  is  one  of  the  following! 

HCA$; 

1 1 

OC^  ^CCH 


UL,6n5  * 

HC  ^ juL  Hts  / 

1 I 

•3 

on  cc6h5 

* See  table  for  references. 


1 


I 


The  following  equation  expresses  the  reaction  "between 
ethyl  acetoacetate  and  ethyl  phenylpropiolate , 


= _|_ 


COOCpH^ 

„ l 

•COCH3 

COOC2H5CHCOCH3 

r*  n rTTr. 

HCT  xfCOOCoKr 


OC  /CCH3 


4- 


Ethyl -4-phenyl -6 -methyl  alpha  pyrone  5-carhoxylate 

(XVITl) , 

The  halogen  derivatives  of  the  alpha  pyrone  compounds 
were  obtained  by  direct  chlorination  or  bromination  of  the 
acids  and  esters.  In  some  instances , as  for  example, in  carrying 
out  the  chlorination  of  methyl  counalinate, solvents  were  used 
such  a.s  carbon  tetrachloride  saturated  with  chlorine. 

Coumalin  (XIX)  the  simplest  of  the  alpha  pyrones  was 
prepared  by  H.v  Pechmann  by  the  dry  distillation  of  mercurous 
coumalinate  in  an  atmosphere  of  hydrogen. 


o 


I 

EC  XCCOOH 

1 1 

0CV  J3H 
C 

M. P.205-2 10 

Soluble  in  methyl 

alcohol, acetic 
acid, ether , water 
and  acetone. 

Per. 17,2334 

II 

HC^^CH 

1 1 

OGv  CCOOH 

cr 

M. P.227-228 

Soluble  in 

alcohol, acetic 
acid, water, and 
acetone . 

J.G.S. 1901 
T.Pt. 2, 1280 

ITT 

VI  CHoCOOH 
HC  XCCOOH 

1 II 

OC.  ilCHpCOOH 

M.P. 185 

Turns  dark 
at  150 

Soluble  in  water 
and  alcohol. 

Annalen  261 
190-208 

IV 

>Xk3 

HC  xC.COOH 
°G  .CCH, 

No 

M.P. 50 

Annalen  261 
190-202 

V 

(\  TT 

HG^CCOOSH* 

1 1 

oa  jch 

M.P. 74 

B.P-60  178-8 

Soluble  in  ether, 
alcohol , acetone 
and  water. 

Annalen  264 
271 

VI 

CH 

HG^  xCGOOC2H5 

1 II 

OCv  GH 

C 

M.P. 36 

B. P.262-265 

Soluble  in  ether, 
alcohol , ace tone 
and  water. 

Annalen  264 
26 1 -309 

VII 

>CH 

HC  XGH 

1 II 

OCv  .CCOOCpHc 
0 

M.P. 59-60 

Soluble  in  water, 
and  in  most 
organic  media. 

J . C . S . 1 90 1 
T.Pt. 2 1280 

VIII 

fITT 

Cl  CT  13C00H 

1 » 

°VCH 

M.P. 187-139 

Soluble  in  acetic 
acid, alcohol  and 
ether. 

Ser.37, 

3329-36 

IX 

/ITT 

Gl(/  XCCOOCKj, 
OC  GH 

M.P. 134-136 

Soluble  in 
chloroform, acetone 
acetic  acid, and 
benzol . 

Ber. 17, 

2396-2399 

X 

Br(X  ^CCOOH 

1 II 

°\/H 

vj 

M.P. 17 6 

Soluble  in  ether, 
alcohol , chloroform 
and  glacial  acetic 
acid 

Ber. 17, 

2396-2399 

XI 

CCH3 

Br”f  TICOOH 

1 II 

OC.  .CGK3 

x> 

M.P . 16 1- 162 

Soluble  in  alcohol 
and  benzene. 

Ber . 26 , 
746-747 

XII 

BrC^^COOOCoHc 

1 II 

OC  /JCH^ 

X) 

M.P. 72 

Ber .35, 
782-790 

XIII 

n t r 

ojrl 

BrC^  XJCOOCoHc 
1 1 
c v/ :H 

M.P. 94-95 

Soluble  in  alcohol 

Annalen  331 
367-364 

XIV 

GH 

HC^  uH 

l I 

OC  /CC^ 

TJ 

M.P. 66-68 

Soluble  in  ether, 
alcohol, acetic 
acid  and  water. 

Ber . 27, 

841-850 

4 


XV 

J \ 6 5 
Her  Ncc,qHR 

1 1 

0CX  /CCfiKcj 
0 

M.P. 245-246 

Soluble  in  glacial 
acetic  acid. 
Insoluble  in  water 
or  alcohol. 

J . G . S . 1 9 1 0 
T.457. 

XVI 

J$6*5 

KCT  xC(COGHq) 

1 I 

oc.  >gch3 

No 

M.P. 128 

J.C.S. 1899, 
T . 4 1 1 . 

XVII 

HCT  nC(COG5H5] 
VCH  3 

■ I. P. 143-144 

J.C.S. 1899, 
T . 4 1 1 

XVIII 

HC^'  N$C§OC?He 

1 1 

°%/gsh3 

M.P. 104 

Ber.35, 

782-790 

XIX 

H /%H 

1 I 

C\./" 

u 

B.?.2G6-9d 

l'„T  T5  q 

B^P.30  '3° 

Miscible  v/ith  all 
ordinary  solvents. 

Annalen  26 4 
P.6 1 -309 

theoretical 

Franz  Feist  treated  bromo-isodehydraeetie  acid  with, 
potassium  hydroxide  and  obtained  a furane  derivative. 

,0. 


C CHts 

BrC^  XCC00H 


x X 3 


-I- 


/ITT.  /t 


'ch3 


2:4  dime thy 1 furane - 3 - c ar boxy lie  acid 
He  then  treated  ethyl-bromo-isodehydracetie  ester  with  potassium 
hvdroxide  and  obtained  a cyclo  propene  derivative. 


/CCH3 

BrC^  hCOOC 


\.x 


+- 


L C00HC1I  -p  CO  OH 

->  CH^cf  +-  \/ 

C Ch- 
ile thy 1-cyclo-propene 
di carboxylic  acid 


\ TT 

on 


methyl-bromo-coumalinate  expectng  to  obte 


ate  a 

simpler  i 

alpha  pyrone 

to  ob 

tain  cy 

clo-propene 

from 

the  e thy 1 

-bromo= 

isodehydracetic  ester. 


BrC^  \IC00CHt5 


4- 


nun 


CC  XCH 


0 


4~ 


\/ 


Instead  he  obtained  a furane  derivative. 

HO 


/ > 


J 


+ 3K0H 


°\/H 


— CH,0It  + 


Oil 


T -T  f 

" :c  -h  1 


,0. 


:ccck 


COOHC 


"CCOOH 

ll 

CK 


Furane  2:4  di carboxylic  acid. 
Since  methyl-chlorocoumalinate  (IX)  prepared 


n-ir 


o 


* 


' 


- 


C*  J 


. 


J . 


v.Pechmann  and  Mills, was  never  converted  either  into  the 
cyclo-propene  derivative  nor  into  the  furane  derivative. 

There  existed  a curiousity  as  to  which  of  the  two  derivatives 
it  would  give  on  treatment  with  potassium  hydroxide, which 
therefore  led  to  this  investigation. 


7 


EXPERIMENTAL 

Coumalinic  acid: -H.v.Pechmann  prepared  coumalinic 
acid  (I)  "by  he*  ' Lalie  acid  (50  grams)  t ter  bath 

with  a mixture  of  (75  grams)  concentrated  sulphuric  acid  and 
(75  grams)  fuming  sulphuric  acid  containing  10-12  per  cent 
sulphur  trioxide,  mien  the  evolution  of  carbon  dioxide  ceased 
in  11/2-2  hours, the  solution  was  carefully  mixed  with  ice 
(2C0  grams)  and  kept  over  night.  The  Precipitated  acid  v:r, 
separated  by  filtration, ’washed  with  ice  water  until  almost 
free  from  sulphuric  acid  and  then  dried  on  porous  piate& * 

The  acid  in  the  mother  liquors  and  washings  was  extracted  by 


shaking  six  times  with  ether.  The  total  yield  of  tne  crude 
product  was  about  80  per  cent, but  it  contained  funaric  acid 
and  traces  of  trimesic  acid.  It  was  purified  by  dissolving 
in  water  between  70-80  degrees, shaking  the  solution  with 
animal  charcoal, and  then  extracting  the  acid  with  ether.  It 
crystallized  from  from  methyl  alcohol  and  glacial  acetic  acid 
in  colorless  prisms, and  on  heating  turned  red  at  200  degrees, 
and  melted  between  2G5~81Q  degrees  with  decompositio  ° 
boiled  at  218  degrees  under  a pressure  of  120  mnu.viuh  pa;  tied. 

de  c ompo  s i t i on . 

As  fuming  sulphuric  acid  containing  10-12  per  cent 
sulphur  trioxide  could  not  be  obtained  in  tne  la^Oi  c,uO.. ; > 
fuming  sulphuric  acid  containing  7 per  cent  sulphur  trioxi-.e 
was  used  and  the  amount  per  50  grams  of  malic  acid  was 
calculated.  A mixture  of  (40  grains)  concentrated  sulphuric  • cid 
and(1l0  grams)  of  fuming  sulphuric  acid  7 per  cent  su_p  ' 


o 


trioxide  was  used, and  procedure  as  given  by  v.Pechmann  was 
carried  out.  An  Cp  per  cent,  yield  of  crude  product  was  obtained 
but  could  not  be  purified  according  to  v.Pechmann ' s method. 
Different  methods  of  purification, and  such  solvents  as  alcohol, 
chloroform, acetone, ether, petroleum  ether  and  ethyl  acetate 
were  tried  but  colorless  prisms  could  not  be  obtained. 

By  dissolving  the  crude  acid  in  hot  glacial  acetic 
acid  and  allowing  it  to  cool  the  coumalinic  acid  crystallized. 
The  crystals  had  a yellowish  color, and  no  definite  shape.  The 
yield  of  pure  acid  was  6 3 per  cent. 


Methyl  Coumalinate . 


Methyl  coumaliriate  ) was  prepared  hy  H.V.Pechmann 
hy  adding  to  one  pa.rt  of  the  acid  2 parts  of  sulphuric  acid 
and  heating  for  15  minutes.  Then  adding  one  part  of  methyl 
alcohol  and  refluxing  for  one  hour  on  a water  hath . After 
cooling  it  was  poured  into  water  and  filtered  to  remove  fumaric 
ester  and  trimesic  ester.  The  filtrate  was  extracted  12  times 
with  ether, dried, the  solution  evaporated  and  the  remaining 
substance  crystallized  in  long  needles.  It  was  recrystallized 
from  hot  water, ether  or  ligroin.  The  yield  was  75  to  35  per- 
cent of  the  weight  of  acid  used, and  the  melting  point  was 
from  75-74  degrees. 


Four  methods  of  preparing  the  ester  were  tried. 

( 1 ) The  method  used  hy  H.V.Pechmann;  (2)  By  passing  dry  hydrogen 
chloride  into  a mixture  of  acid  and  methyl  alcohol;  (5)  "y 
treating  the  silver  salt  of  the  acid  with  methyl  iodide; 

(4)  By  passing  methyl  alcohol  vapors  through  a mixture  of  aci a, 
sulphuric  acid  and  methyl  alcohol. 

(1)  After  following  v.Pechmann's  method  of  preparation, 
methyl  coumalinate  melting  from  72-73  degrees  was  obtained. 

The  best  yield  obtained  in  a half  dozen  trails  was  4a  per  cent 
of  the  weight  of  acid  used. 

(2)  One  part  of  the  acid  was  added  to  one  part  of 
methyl  alcohol  and  dry  hydrogen  chloride  was  passed  in  until 


the  solution  was  completely  saturated. . The  solution  was  poured 
into  water  and  filtered.  The  filtrate  was  extracted  12  times 
with  ether, washed  with  a dilute  solution  of  sodium  carbonate 


;0 


then  dried  with  calcium  chloride.  The  solution  was  evaporated 
and  a brown  sticky  substance  remained  that  could  not  be 
crystallized.  Later  it  was  concluded  that  if  the  mass  were 
distilled  under  diminished  pressure  methyl  coumalinate  would 
be  obtained. 

(3)  10  grams  of  coumalinic  acid  was  dissolved  in 
ammonia  water, made  almost  neutral  with  nitric  acid  and  silver 
nitrate  added.  The  silver  salt  was  filtered  off  and  placed 
into  a flask  connected  to  a reflux  condenser.  Ether  and  methyl 
iodide  were  added  respectively  and  the  solution  was  permitted 
to  reflux  for  three  hours.  After  evaporating  the  ether  solution 
a brown  mass  remained  which  could  not  be  crystallized. 

(4)  To  30  grams  of  coumalinic  acid  and  6 cc. 
sulphuric  acid,60  cc.  of  methyl  alcohol  was  e.dded.  Absolute 
methyl  alcohol  vapors  were  passed  through  the  mixture  removing 
the  water  formed  in  the  reaction.  TTnen  the  reaction  was 
complete , the  solution  was  cooled, poured  into  water  and  the 
oil  layer  was  separated  from  the  water  layer.  The  water  layer 
was  extracted  twelve  times  with  ether, made  neutral  by  washing 
with  a dilute  solution  of  sodium  acid  carbonate , dried  with 
calcium  chloride  and  the  ether  evaporated.  The  resulting 
material  was  distilled  under  diminished  pressure.  Methyl 
coumalinate  distilled  over  between  170-130  degrees  and  -0  mm. 
Melting  point  of  the  ester, 73-74  degrees.  The  oil  layer  on 
distillation  gave  6 grams  of  methyl  coumalinate.  Total  yield 
of  ester  was  48  per  cent  of  the  weight  of  acid  used. 


' Me  thy  1 - chi  or  o c oumalinate 


To  30  grains  of  pure  methyl  coumalinate  (30, the 
calculated  amount  of  carbon  tetrachloride  saturated  with 
7-8  per  cent  chlorine  was  added  and  allowed  to  stand  at  room 
temperature.  After  two  or  three  days  hydrogen  chloride  started 
to  be  given  off  and  crystals  formed.  The  crystals  were  separated, 
and  washed  with  ether.  The  crude  product  (25  grams)  was  then 
re crystallized  from  alcohol.  17  grams  of  pure  chloro-ester 
melting, 134- 136  degrees  was  obtained. 

This  method  was  tried  about  a dozen  times  with  5 to 
10  grams  of  pure  methyl  coumalinate  and  the  best  yield  obtained 
was  one  gram  of  pure  methyl-—  chlorocoumalinate  for  every  10 
grams  of  methyl  coumalinate.  The  crude  product  obtained  melted 
between  94-103  degrees, but  after  re crvs tall i zing  three  times 
from  alcohol, a pure  product  melting, 133=*  135  degrees  was  secured. 

Sulphuryl  chloride  was  tried  instead  of  carbon  tetra- 
chloride but  the  yield  was  not  increased. 


■ 


I 


. 


# Furane  2:4  di carboxylic  acid. 


Meth.yl-bromocoumalin.ate  (5grams)  were  mixed  in  a cold 
solution  containing  (10  grams)  potassium  hydroxide  in  (20  grams) 
of  water.  It  was  heated  for  twenty  minutes, allowed  to  cool  and 
then  neutralized  with  sulphuric  acid.  The  whole  mass  was  placed 
on  a water  bath  to  dry.  The  brown  mass  remaining  was  extracted 
with  acetone.  After  vaporising  the  acetone  a brown  mass  remained 
which  was  washed  with  ligroin  and  recrystallized  from  hot  water. 
The  yield  was  3*7  grams , melting  at  266  degrees. 


TIhen  2 grams  of  methyl-chlorocoumalimate  was  obtained, 
the  procedure  as  given  above  was  followed  through.  The  brown 
mass  obtained  after  vaporizing  the  acetone  was  insufficient  to 
carry  the  operation  any  further.  Lack  of  time  prevented  the 
preparation  of  more  methyl-chlorocoumalinate; thus  the  problem 
had  to  be  left  without  a definite  conclusion. 


* Franz  Feist,  Ber. 34, 1992-1994. 


13 


.. 

- 


. 


rt  rr«-ir«  W 

ijUiVU'.iiij;  lX 


Coumalinic  acid  was  prepared  in  better  yields  than 
that  recorded  in  the  literature. 

The  acid  was  esterified  using  sulphuric  acid  as  a 

catalyst. 

Difficulty  was  experienced  in  preparing  methyl- 
chloro-coumalinate  in  sufficient  quantities  to  work  with. 

One  experiment, methyl-chloro-coumalinate  plus  potassium 
hydroxide  gave  no  solid  product. 


14 


